History of maternal fetal loss and increased risk of childhood acute leukemia at an early age. A report from the childrens cancer group

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Abstract
Background. Maternal reproductive history of fetal loss previously has been reported to be associated with an increased risk of leukemia in subsequent offspring. Data from a Childrens Cancer Group (CCG) case‐control study were analyzed to test the hypothesis that this association was dependent on the number of previous fetal losses age at leukemia diagnosis. Methods. A case‐control study using a large Childrens Cancer Group database examined maternal history of fetal loss as a risk factor for childhood leukemia in subsequent offspring. One thousand seven hundred fifty‐three patients with childhood acute leukemia were compared with 839 community control subjects s and 2081 nonleukemia cancer control subjects. Results. A modest increase in risk was found to be associated with a history of fetal loss. Stratification by age at diagnosis of leukemia showed that this association was significant only for those patients diagnosed before 4 years of age and most significant in those patients diagnosed before 2 years of age. When comparing community controls with patients acute lymphocytic leukemia diagnosed before 2 years of age, one previous fetal loss was associated with a five‐fold increased risk (P < 0.001) whereas two or more fetal losses were associated with a relative risk of 24.8 (P < 0.001). Similarly, patients with acute myelocytic leukemia diagnosed before 2 years of age demonstrated 5‐fold and 12‐fold increased risks associated with the previous fetal loss and 2 or more previous fetal losses, respectively. Conclusions. Childhood acute leukemia occurring at younger ages may be associated with an underlying genetic abnormality or chronic environmental exposure, which can be either lethal to the developing fetus or mutagenic and result in the development of acute leukemia.